Pharma Manufacturing

Examining the landscape of pharmaceutical manufacturing in 2015.

If behavior often speaks volumes, then the pharmaceutical industry is saying a lot lately in the way that it is responding to the social and economic forces that affect its markets and the potential commercial success of the drugs they develop and deliver around the world.
This two-piece State of the Union series features:• Industry Voice: Pharma leadership talks strategy • In it for the Long Haul: PhM's 2015 Reader Salary Survey Results

Chad Juros inspired the crowd with his story and his magic, but closed his talk by saying, "The true magicians in this world are those who are bringing these miracle treatments and services that saved my life."

The start of the 2015 Annual Meeting was magic…literally. Chad Juros, founder of the Spread the Magic Foundation, a nonprofit corporation that performs magic to raise money for pediatric cancer patients, started the three-day conference with a message of positivity and gratitude. A childhood cancer survivor and medical miracle, Chad’s father taught him magic as a survival tactic, a way of diverting attention from the negative to the positive in his life. But as accomplished as he is, Chad closed his speech by admitting he, in fact, does not know “real” magic. “The true magicians in this world are those who are bringing these miracle treatments and services that saved my life,” Chad said. “I’m living proof that the hard work…

Pharma can take inspiration from industries with mature quality systems and advanced quality capabilities

Quality has a special meaning in pharmaceuticals, where production or distribution errors can jeopardize human life. But other industries face similar challenges, and some have developed sophisticated quality systems. As pharmaceutical companies look for ways to improve their quality practices and performance, they can take ideas from these quality leaders and adapt them for pharma.
Quality can be defined in various ways, from “fitness for purpose” to “meeting customer expectations” to predictability in statistical terms. Each industry understands quality differently, and priorities depend on the specifics of products and markets. In the automotive industry, for instance, companies generally define quality as the ability to meet…

Advancing aseptic processing through the use of robot technology

Josh Russell, AST’s Life Science project manager, has been an advocate for advancing aseptic processing through the use of robot technology for years, writing about its benefits and exploring their application in their customer’s solutions. According to Russell, aseptic manufacturing generally entails often repetitive activity that requires a high degree of reproducibility in order to create a high-quality product. He asserts that robots are the ideal platform to perform the highly accurate, repeatable operations demanded by aseptic processing operations. These non-organic automatons have the distinction of being able to operate where no man should or can. “This becomes particularly important in applications that require…

If your equipment is not ready, it’s time to get it ready

Pharmaceutical counterfeiting is on the rise — and a growing health and safety issue with deep consequences for consumers and drug manufacturers alike. A number of factors contribute to counterfeiting, including:
• Increased involvement of under-regulated wholesalers and repackagers in the supply chain,• Proliferation of online pharmacies,• Counterfeiting technology advancements, and• Increased importation of gray-market medicines.
To combat counterfeiting, pharmaceutical manufacturers are putting serialization processes in place — whereby each item is assigned and marked with a unique serial number. Drug makers can then identify and track each unit throughout the supply chain, providing greater visibility and traceability.
But…

The optimization and scale-up of wet granulation processes is often an essential step in the commercialization of oral solid dosage (OSD) products. Granulation enables the preparation of an optimized blend for tableting in which small quantities of highly potent active ingredients (APIs) are stably and homogeneously distributed. Furthermore, granule properties can be manipulated to control, for example, the flowability of the blend and its compressibility. In these ways granulation underpins the manufacture of high-quality tablets with consistent dose uniformity.Wet granulation, and in particular high shear wet granulation, is the technology of choice for many OSD production processes. Compared with alternative methods, high shear…

Novel technologies open a new avenue for developing the future
of pharmaceutical manufacturing

Pharmaceutical manufacturing has been performed using batch technologies for more than a century. While most other manufacturing industries use continuous operations combined with advanced process control and automation, the pharmaceutical industry…

The optimization and scale-up of wet granulation processes is often an essential step in the commercialization of oral solid dosage (OSD) products. Granulation enables the preparation of an optimized blend for tableting in which small quantities of highly potent active ingredients (APIs) are stably and homogeneously distributed. Furthermore, granule properties can be manipulated to control, for example, the flowability of the blend and its compressibility. In these ways granulation underpins the manufacture of high-quality tablets with consistent dose uniformity.Wet granulation, and in particular high shear wet granulation, is the technology of choice for many OSD production processes. Compared with alternative methods, high shear…

Closed-loop systems help pharmaceutical manufacturers save water and energy

While the pharmaceutical industry continues on its road to recovery, sustainability will remain a priority for pharmaceutical manufacturers as they strive for profitable growth. One way many can make significant headway toward true sustainability — and improve the bottom line — is through the use of advanced, closed-loop process cooling technology specifically designed to lower water consumption and save energy.
Process cooling efficiency should be on the front burner rather than the afterthought it often is. Doing so is particularly important today given increasing concern over water use by pharmaceutical manufacturers and other companies that use water-intensive processes to make and deliver products. Following are some…

Recent

When the FDA finds significant departures from good clinical practice, those findings are seldom reflected in the peer-reviewed literature, even when there is evidence of data fabrication or other forms of research misconduct.

A new New York University analysis found that when the FDA's finds serious problems with how medical researchers collect their data, the peer-reviewed literature often doesn't mention it.Using documents and data from 1998 to 2013, researchers identified 57 clinical trials that received an “official action indicated” violation for reasons including inadequate or inaccurate recordkeeping, false information and poor patient safety.
And yet, among the 78 published analyses of data from those sanctioned trials, only three noted violations.
One example was found where the entire clinical trial was deemed unreliable by the FDA, and the published paper failed to make mention of this. In another example, the published paper claimed all…

New xCELLigence RTCA CardioECR is the first platform for simultaneous measurement of Cardiomyocyte Contractility and Electrophysiology

Responding to the need for more predictive preclinical assays for cardiac liability, ACEA Biosciences introduced a “ground-breaking” device the company describes as “next generation.” Designated the xCELLigence RTCA CardioECR System, it is…

Heard it on DCAT Street: Pharma leadership talks strategy at one of the industry’s oldest gatherings.

If behavior often speaks volumes, then the pharmaceutical industry is saying a lot lately in the way that it is responding to the social and economic forces that affect its markets and the potential commercial success of the drugs they develop and deliver around the world. It’s the Pharma industry’s voice, articulating its direction, its strategies and its aspirations using a familiar, but sophisticated commercial vocabulary learned over its long history. Certainly the “Industry” speaks with many tongues, but its ongoing dialogue was recently articulated by thought leaders meeting and presenting at DCAT Week 2015. Celebrating its 125th year, the Drug, Chemical & Associated Technologies Association meeting may likely be one of…

Chad Juros inspired the crowd with his story and his magic, but closed his talk by saying, "The true magicians in this world are those who are bringing these miracle treatments and services that saved my life."

The start of the 2015 Annual Meeting was magic…literally. Chad Juros, founder of the Spread the Magic Foundation, a nonprofit corporation that performs magic to raise money for pediatric cancer patients, started the three-day conference with a message of positivity and gratitude. A childhood cancer survivor and medical miracle, Chad’s father taught him magic as a survival tactic, a way of diverting attention from the negative to the positive in his life. But as accomplished as he is, Chad closed his speech by admitting he, in fact, does not know “real” magic. “The true magicians in this world are those who are bringing these miracle treatments and services that saved my life,” Chad said. “I’m living proof that the hard work…

PerkinElmer will provide on-site staff and training as well as scientific application support, a new offering to JLABS residents

Lab solutions provider PerkinElmer Inc. announced its collaboration with Johnson & Johnson Innovation to equip its JLABS @South San Francisco (JLABS @SSF) life science incubator with instruments and lab services to address the research needs of resident startups. Janssen Labs (ostensibly JLABS) is the no-strings-attached incubator network that Johnson & Johnson says, is home to more than 70 life science companies. JLABS @SSF is the newest member of the J&J Innovation JLAB network which includes an established San Francisco location as well as facilities in San Diego, Boston and most recently Houston.Companies seeking to avail themselves of the infrastructure and support apply and go through a selection process which evaluates…

Kythera is a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel prescription products for the aesthetic medicine market. The company’s objective is to develop prescription products using an approach that relies on the scientific rigor of biotechnology to address unmet needs in a rapidly growing market. Kythera’s initial focus is on facial aesthetics — the market’s largest segment. The company’s drug for the reduction of submental fat is currently in late-stage clinical development.
SYSTEM TO IMPROVEKythera sought a system to improve clinical document management and facilitate business processes for the development of its newest product candidate. The company had 26…

According to Johnson & Johnson, the Geel, Belgium facility produces 54 different types of APIs and three semi-finished APIs, via more than 350 different synthesis steps. In total, the Geel produces +/- 60 % of the total small-molecule API volume within the company. Johnson & Johnson recently updated its Manufacturing Execution System (MES) to PAS-X V3.1.5. The Geel site plays a key role for J&J: there, PAS-X is in operation as full-blown MES in several areas of its API manufacturing lines and warehouse operations. About 300 employees use the system, says Werum, to achieve operational excellence and transparency at the 450.821 m2 site.
“Johnson & Johnson has already implemented Werum’s PAS-X in some plants,” says…

Recent

The memorandum of understanding establishes a process of disclosure and sharing of their respective databases

The U.S. Food and Drug Administration (FDA) and the Environmental Protection Agency (EPA) announced they have signed a Memorandum of Understanding to share data on pesticides and toxic substances. This will allow the agencies to more easily share information about risks to the public and the environment.
According to a press release, the FDA and EPA have complementary roles in their regulatory authority for some substances incorporated into food (including animal food and feed), animal drugs and cosmetics. The FDA protects and promotes the public health by enforcing the Food, Drug, and Cosmetic Act, and several related public health laws. EPA manages the pesticides and toxic substances programs under the Federal Insecticide, Fungicide, and…

A new report from FireEye says that a cybercriminal group has been stealing data from more than 100 organizations, mainly targeting publicly traded health care, pharmaceutical and biotechnology companies, to gain insider knowledge to manipulate the stock market.

A new report from U.S. security firm FireEye says that a cybercriminal group known as FIN4 has been stealing data from more than 100 organizations, mainly targeting publicly traded healthcare, pharmaceutical and biotechnology companies, to gain insider knowledge to manipulate the stock market.
FireEye reports that the cybercriminals have targeted the email accounts of individuals privy to the most confidential information of more than 100 companies. According to the report, "FIN4 appears to have a deep familiarity with business deals and corporate communications, and their effects on financial markets. Operating since at least mid-2013, FIN4 distinctly focuses on compromising the accounts of individuals who possess non-public…

Specializing in pain management and fungal disease, Janssen-Cilag Farmacêutica Ltda., is a research-based pharmaceutical company located in São Paulo, Brazil. Janssen-Cilag is a member of the Johnson & Johnson family of companies — the world’s largest personal care and health products manufacturer with worldwide annual sales totaling $63.7 billion. In an effort to streamline business processes, Janssen-Cilag’s Global Pharmaceutical Supply Group (GPSG) Brazil recently adopted a comprehensive enterprise integration solution. As part of its quest for a state-of-the-art IT implementation, GPSG Brazil took advantage of the latest technological advancements from Thermo Scientific in its São José dos Campos laboratory complex in…

Recent

Kemwell Biopharma announced that its oral solids manufacturing facility located in Bangalore, India has successfully completed its second U.S. Food and Drug Administration inspection.

Kemwell Biopharma, a global bio/pharmaceutical contract development and manufacturingcompany, announced that its oral solids manufacturing facility located in Bangalore, India has successfully completed its second U.S. Food and Drug Administration inspection.
This audit took place for an ANDA filed for a customer. On completion of the inspection, the FDA inspector concluded that the facility, systems and practices comply with U.S. FDA requirements and no observations were reported on Form 483.
The state-of-the-art oral solids facility started cGMP production in 2008 and is designed to produce 5 billion tablets and capsules annually. The facility has high flexibility built-in to manage batch sizes ranging from 10kg to 1000kg. Kemwell has…

Pfizer expects to receive a $200 million upfront payment from Lilly in accordance with their collaboration agreement

Pfizer Inc. and Eli Lilly and Company are planning to resume the Phase 3 clinical program for tanezumab. As a result, Pfizer expects to receive a $200 million upfront payment from Lilly in accordance with their collaboration agreement, according to a press release.
This announcement follows a decision by the U.S. Food and Drug Administration (FDA) to lift the partial clinical hold on the tanezumab development program after a review of nonclinical data characterizing the sympathetic nervous system response to tanezumab, the release said. The data were submitted to the FDA in February 2015.
In the prior clinical studies of more than 11,000 patients, tanezumab demonstrated clinically meaningful efficacy vs. placebo and other select commonly…

Is the FDA allowed to approve a use for a treatment for which a drug maker did not seek approval?

Japan's Otsuka Pharmaceuticals is suing the U.S. FDA, claiming the agency illegally broadened the indication for its top-selling Abilify antipsychotic, opening the door to generic competition in the process.
According to the WSJ, the FDA approved Abilify for treating children with Tourette Syndrome last December, a move which delayed generics because the new indication gave Otsuka another seven years of exclusive marketing rights under an orphan designation.
Last month, the FDA notified Otsuka that the added indication for treating Tourette Syndrome would apply to adults as well as children.
By broadening Abilify's indication to include adults, Otsuka argues the FDA will trigger a labeling change that will allow generic competition.

A CPV approach based only on statistical tools addresses only the operational level of the system; management needs to be involved

A company gets a 483 warning letter which, among other things, criticizes the company’s continued process verification (CPV) approach. The observations include inadequate sampling plans, wrong statistical methods used, and company employees do not understand the statistical methods being used. Only a single quality engineer knows how the tools are being used.
So the company scurries about figuring out how to respond including the adoption of better procedures and more clearly explaining the methods being used. So what is the problem here? Who is at fault? The quality engineer? His supervisor? The plant manager? How should this situation be remedied?
The answer is: All of the above with the major portion the responsibility being that of…

Chad Juros inspired the crowd with his story and his magic, but closed his talk by saying, "The true magicians in this world are those who are bringing these miracle treatments and services that saved my life."

The start of the 2015 Annual Meeting was magic…literally. Chad Juros, founder of the Spread the Magic Foundation, a nonprofit corporation that performs magic to raise money for pediatric cancer patients, started the three-day conference with a message of positivity and gratitude. A childhood cancer survivor and medical miracle, Chad’s father taught him magic as a survival tactic, a way of diverting attention from the negative to the positive in his life. But as accomplished as he is, Chad closed his speech by admitting he, in fact, does not know “real” magic. “The true magicians in this world are those who are bringing these miracle treatments and services that saved my life,” Chad said. “I’m living proof that the hard work…

Pharma can take inspiration from industries with mature quality systems and advanced quality capabilities

Quality has a special meaning in pharmaceuticals, where production or distribution errors can jeopardize human life. But other industries face similar challenges, and some have developed sophisticated quality systems. As pharmaceutical companies look for ways to improve their quality practices and performance, they can take ideas from these quality leaders and adapt them for pharma.
Quality can be defined in various ways, from “fitness for purpose” to “meeting customer expectations” to predictability in statistical terms. Each industry understands quality differently, and priorities depend on the specifics of products and markets. In the automotive industry, for instance, companies generally define quality as the ability to meet…

If your equipment is not ready, it’s time to get it ready

Pharmaceutical counterfeiting is on the rise — and a growing health and safety issue with deep consequences for consumers and drug manufacturers alike. A number of factors contribute to counterfeiting, including:
• Increased involvement of under-regulated wholesalers and repackagers in the supply chain,• Proliferation of online pharmacies,• Counterfeiting technology advancements, and• Increased importation of gray-market medicines.
To combat counterfeiting, pharmaceutical manufacturers are putting serialization processes in place — whereby each item is assigned and marked with a unique serial number. Drug makers can then identify and track each unit throughout the supply chain, providing greater visibility and traceability.
But…

A well-designed, reliable raw material storage and conveyance environment can make or break a pharmaceutical manufacturing environment. Raw material storage and conveyance is fundamental to quality assurance and profitability. Increasingly, this environment also has become integral to the rigorous regulatory requirements for tracking and tracing products throughout the supply chain. To meet quality and standardization objectives, a design solution must be based on an overview of the entire process from delivery of raw materials to the manufacturing site to delivery of product ingredients to the manufacturing line. The correct design basis is predicated, particularly, on an understanding of raw material characteristics and facility…

Manufacturing HP active pharmaceutical ingredient drugs is a challenge best met with a thorough assessment of risk and a robust containment strategy

Approximately 25 percent of drugs in development worldwide are classified as highly potent, with this percentage expected to grow over the coming years. A compound is generally classed as highly potent if it has an occupational exposure limit (OEL) of ≤10μg/m3, a daily therapeutic dose of ≤10mg/day or if a 1 mg/kg/day dose produces serious toxicity in laboratory animals. While such highly potent compounds can have significant benefits in the treatment of certain medical conditions, they present substantial challenges to the pharmaceutical industry.
These challenges include:
• Can personnel and the environment involved in the manufacture of high potency products be protected; • Can adequacy of controls preventing contamination of…

Closed-loop systems help pharmaceutical manufacturers save water and energy

While the pharmaceutical industry continues on its road to recovery, sustainability will remain a priority for pharmaceutical manufacturers as they strive for profitable growth. One way many can make significant headway toward true sustainability — and improve the bottom line — is through the use of advanced, closed-loop process cooling technology specifically designed to lower water consumption and save energy.
Process cooling efficiency should be on the front burner rather than the afterthought it often is. Doing so is particularly important today given increasing concern over water use by pharmaceutical manufacturers and other companies that use water-intensive processes to make and deliver products. Following are some…

The new investment in biotechnology will create up to 100 new jobs

AbbVie plans to expand of one of its existing sites in Barceloneta with an estimated investment of $30 million. The expansion will add to Puerto Rico’s capabilities as a manufacturing destination for biotechnology and is expected to create up to 100 new jobs over the next two years, according to a press release.“AbbVie’s expansion in Barceloneta is very important for us, as this site is one of the world's most advanced biopharmaceutical facilities, contributing to our island's growing reputation as a biotech hub,” said Puerto Rico governor Alejandro García Padilla.
According to Stephen Muldoon, vice president of engineering and operations for AbbVie, “This investment demonstrates our commitment to Puerto Rico as a key element of…

Closed-loop systems help pharmaceutical manufacturers save water and energy

While the pharmaceutical industry continues on its road to recovery, sustainability will remain a priority for pharmaceutical manufacturers as they strive for profitable growth. One way many can make significant headway toward true sustainability — and improve the bottom line — is through the use of advanced, closed-loop process cooling technology specifically designed to lower water consumption and save energy.
Process cooling efficiency should be on the front burner rather than the afterthought it often is. Doing so is particularly important today given increasing concern over water use by pharmaceutical manufacturers and other companies that use water-intensive processes to make and deliver products. Following are some…

Recent

Heard it on DCAT Street: Pharma leadership talks strategy at one of the industry’s oldest gatherings.

If behavior often speaks volumes, then the pharmaceutical industry is saying a lot lately in the way that it is responding to the social and economic forces that affect its markets and the potential commercial success of the drugs they develop and deliver around the world. It’s the Pharma industry’s voice, articulating its direction, its strategies and its aspirations using a familiar, but sophisticated commercial vocabulary learned over its long history. Certainly the “Industry” speaks with many tongues, but its ongoing dialogue was recently articulated by thought leaders meeting and presenting at DCAT Week 2015. Celebrating its 125th year, the Drug, Chemical & Associated Technologies Association meeting may likely be one of…

New York-based Synergy Pharmaceuticals, developer of gastrointestinal disorder drugs, is talking to advisers about a potential sale of the company, according to Bloomberg sources.

New York-based Synergy Pharmaceuticals, developer of gastrointestinal disorder drugs, is talking to advisers about a potential sale of the company, according to Bloomberg sources.
Earlier this month, Salix -- which competes with Synergy in the gastrointestinal field -- was purchased by Valeant Pharmaceuticals for $10 billion.
Bloomberg sources say the sale of Synergy may depend on the results of a late-stage trial of IBS drug plecanatide, which should be announced in May.
Read the Bloomberg article

This comes on the heels of GSK announcing 150 layoffs in Pennsylvania

GlaxoSmithKline announced another round of layoffs affecting 180 workers in North Carolina, according to an article in the Triangle Business Journal. Eliminated positions were in sales, marketing, operations and other managerial, technical and support roles, the article said. This comes on the heels of GSK announcing 150 layoffs in Pennsylvania. Read the full story

Is the FDA allowed to approve a use for a treatment for which a drug maker did not seek approval?

Japan's Otsuka Pharmaceuticals is suing the U.S. FDA, claiming the agency illegally broadened the indication for its top-selling Abilify antipsychotic, opening the door to generic competition in the process.
According to the WSJ, the FDA approved Abilify for treating children with Tourette Syndrome last December, a move which delayed generics because the new indication gave Otsuka another seven years of exclusive marketing rights under an orphan designation.
Last month, the FDA notified Otsuka that the added indication for treating Tourette Syndrome would apply to adults as well as children.
By broadening Abilify's indication to include adults, Otsuka argues the FDA will trigger a labeling change that will allow generic competition.

Johnson & Johnson subsidiary McNeil Consumer Healthcare pleaded guilty on Tuesday to selling liquid medicine contaminated with metal and agreed to pay $25 million to resolve the case, says the U.S. Department of Justice.
According to court documents, on or about May 1, 2009, McNeil received a complaint from a consumer regarding the presence of “black specks in the liquid on the bottom of the bottle” of Infants’ Tylenol. The foreign material was later identified as nickel/chromium-rich inclusions, which were not intended ingredients in the drug.
In connection with receiving this consumer complaint, McNeil did not initiate or complete a Corrective Action Preventive Action (CAPA) plan, as alleged in the charging document. The…

As PTFE diaphragms are subjected to more aggressive sterilization and cooling conditions, they are more prone to failure from cracking, splitting, deformation and SIP steam-induced blisters.

Steam-in-place (SIP) sterilization is an essential process in the pharmaceutical and biotechnology industries. The American Society of Mechanical Engineers Bioprocessing Equipment (ASME-BPE) standard recommends diaphragm valves for aseptic and sterile systems. Weir-type sanitary valves with polytetrafluoroethylene (PTFE) diaphragms are most commonly used in these systems, but sanitary diverter valves and valves with hermetic PTFE diaphragm stem seals are also used extensively.

Typical SIP cycle temperature parameters are 120°C to 135°C at corresponding saturated steam pressure, with exposure time dependent on system design and complexity [1]. The ASME-BPE 2009 Standard Appendix J for simulated SIP cycle parameters calls for minimum 130°C steam and one hour exposure [2]. Overkill SIP parameters are minimum 140°C steam for two to four hours exposure. These SIP cycles are cooled slowly with pressurized clean air.

To achieve more frequent batch changes and greater production yields, some in the pharmaceutical industry have begun to use high-temperature, short-time (HTST) sterilization systems with SIP temperatures ranging from 140°C to 160°C [3]. These SIP cycles are cooled more quickly with air or water, often resulting in blistering of PTFE diaphragms, posing sterility problems if not detected early enough and reducing their service lives.

Recently, we did our own experimentation to investigate this phenomenon. This article will discuss the types of valves and diaphragms tested, the test equipment and procedures used, analysis of blistered PTFE diaphragms, the mechanics of blister formation, and what can be done to alleviate it.

Diaphragm VariabilityModern pharmaceutical and bioprocessing plants have large aseptic systems of vessels, fermentors and bioreactors interconnected by a maze of piping. Integral to these systems are diaphragm valves, which the ASME-BPE standard recommends for pharmaceutical and bioprocessing applications with product contact [2]. The types of diaphragm valves recommended are weir-type, diverting and other two-piece stem and plug valves with diaphragm stem seals.

The most commonly used diaphragm valves are weir-type (Figure 1). These valves provide the self-draining capability required for hygienic processing. Usually made of 316L stainless steel, the valves are supplied with either manual or automated actuators.

The heart of a weir valve is the PTFE diaphragm. As shown in Figure 1, the two-piece diaphragms consist of a PTFE face layer and EPDM elastomer backing, which provides resiliency and compression during valve actuation. Having no center hole, the PTFE diaphragm isolates the product from the valve stem and actuator mechanism. PTFE diaphragms are used in critical, high-temperature SIP applications and with harsh chemicals.

Figure 1. Weir-type Sanitary Valve with PTFE/EPDM Diaphragm

PTFE polymers are known for their high purity, exceptional non-adhering properties, chemical resistance, and temperature capabilities up to 260°C. These polymers have ultra-low-level extractables, conforming to FDA 21 CFR 177.1550 and USP28 Class VI Part 87 and 88. Chemically, biochemically, and enzymatically inert, they have wide acceptance in pharmaceutical and biotechnology industries.

PTFE polymers are grouped into two types: conventional, which are white in appearance, and modified, which are more translucent. Containing up to one percent perfluoropropyl vinyl ether (PPVE), modified PTFE compounds represent the next generation of PTFE polymers, available in a number of different grades. Compression molded parts of modified PTFE have a lower percentage of voids and lower permeation rates for liquid and vapor chemicals and helium gas. Modified PTFE diaphragm disks typically offer a 30% reduction in permeability for different chemicals [4].

Pictured in Figure 2 are conventional and modified PTFE diaphragms for weir-type valves. The diaphragms are manufactured by compression-molding powder resin, followed by sintering. The threaded drive stud in the center is usually a molded-in metal bolt or machined from PTFE stock, as seen in the round conventional PTFE diaphragm. Some valve manufacturers mold their own diaphragms, while others purchase them from distributors. Pharmaceutical and bioprocessing facilities also purchase replacement diaphragms based on published dimensional specifications, service temperature ratings, and certification of conformance to applicable FDA and USP regulations. Distributors publish maximum intermittent steam temperatures or SIP sterilization capabilities up to 165°C for PTFE/EPDM diaphragms.

Differences in production processes and grades result in PTFE diaphragms with different performance properties and durability. PTFE diaphragms manufactured by some processes cannot withstand high-temperature applications or meet the demands of SIP sterilization.

Diaphragm Integrity and PerformanceSIP cycles consist of three stages—heat-up, hold/exposure and cool-down. During the heat-up stage, saturated steam is injected, and the equipment with valves is heated to the required sterilization temperature. This stage is complete when the cold spot in the system—usually the condensate drain, dead leg, tank bottom, or furthest location from steam inlet—reaches the pre-set sterilization temperature. When a thermocouple probe at the slowest heating location reaches this temperature, the hold or exposure stage begins, during which both pressure and temperature must be accurately controlled. Exposure time is typically 30 to 45 minutes at 20 to 30 psi with corresponding steam temperatures of 121°C to 135°C [5]. For systems with hard-to-access areas, exposure times will be longer.

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